Background:

Disease Activity Score (DAS) and its modified versions, Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) are indices used to measure disease activity. Provided thresholds for activity states to adjust therapy on were solely based on rheumatologists decisions. To achieve disease remission, treatment adjustments based on tight controlled indices is recommended in individual patients, but no preferred index is defined. Moreover, data on reflection of disease state with clinical remission are missing.

Purpose:

To investigate the interchangeability of measures of disease activity to base treatment decisions on. To compare remission thresholds of indices with predefined clinical remission.

Methods:

For this study data are used of a currently ongoing clinical trial in patients 18 years or older with recent-onset arthritis (tREACH). Treatment decisions to step up or step down are performed every 3 months and based upon the DAS thresholds >2.4 and <1.6. For the present study DAS indices are recalculated, namely DAS 3 variables (no patient Global), DAS-CRP, DAS-CRP 3 variables, same combinations for 28 joints and SDAI and CDAI. Thresholds for remission and active disease for DAS28, SDAI and CDAI are respectively <2.6 and >3.2, <3.30 and >11, and <2.80 and >10. Clinical remission is defined as having: (1) less than 2 swollen joints, (2) no swollen joints and (3) no swollen and no tender joints. Discriminative ability of thresholds were calculated by sensitivity and specificity analyses using DAS as reference.

Results:

753 disease activity scores per index were available from 344 patients using data of all visits available. Active disease states of various indices compared to DAS have a sensitivity range from 78% to 90%. DAS indices with 44 joints have a specificity above 95%, others are below 90% (Table 1). For remission all DAS indices have a sensitivity above 82% whereas CDAI and SDAI have a significant lower sensitivity of respectively 28% and 26%. For specificity the indices varied not statistical significantly (Table 1).

SDAI and CDAI have a significant lower sensitivity and high specificity for clinical remission. All DAS indices however have a higher sensitivity but lower specificity (Table 2).

Conclusion:

Various indices of disease activity misclassify disease state when compared to the original DAS, which could imply that patients have still active disease in one while not in another. Moreover remission thresholds are also discordant where SDAI and CDAI under detect clinical remission, where DAS indices might misclassify patients to be in clinical remission.

Table 1. Discriminative ability of indices using original DAS as reference

n=344 providing 753 time points

Rheumatoid Arthritis* (n=92 in 283 time points)

Sensitivity (95% CI)

Specificity (95% CI)

Sensitivity (95% CI)

Specificity (95% CI)

DAS (CRP)>2.4

0.84 (0.780.88)

0.96 (0.940.97)

0.78 (0.670.87)

0.96 (0.930.98)

DAS (3var)>2.4

0.89 (0.840.93)

0.99 (0.971.00)

0.89 (0.800.95)

0.99 (0.971.00)

DAS (CRP/3var)>2.4

0.78 (0.720.84)

0.97 (0.950.98)

0.76 (0.640.85)

0.98 (0.950.99)

DAS28 >3.2

0.91 (0.860.95)

0.81 (0.770.84)

0.97 (0.911.00)

0.79 (0.730.84)

DAS28 (CRP)>3.2

0.88 (0.830.92)

0.84 (0.810.87)

0.91 (0.820.96)

0.85 (0.790.89)

DAS29 (3var)>3.2

0.87 (0.820.91)

0.84 (0.810.87)

0.95 (0.870.99)

0.84 (0.780.88)

DAS28 (CRP/3var)>2.4

0.79 (0.730.84)

0.88 (0.850.91)

0.85 (0.750.92)

0.89 (0.840.93)

SDAI>11

0.89 (0.840.93)

0.73 (0.690.76)

0.93 (0.850.98)

0.75 (0.680.80)

CDAI>10

0.90 (0.850.93)

0.74 (0.700.78)

0.95 (0.870.99)

0.76 (0.700.82)

DAS (CRP) <1.6

0.90 (0.860.93)

0.94 (0.910.96)

0.93 (0.870.97)

0.91 (0.860.95)

DAS (3var) <1.6

0.95 (0.920.97)

0.97 (0.950.98)

0.95 (0.900.98)

0.96 (0.920.99)

DAS (CRP/3var) <1.6

0.90 (0.860.93)

0.93 (0.900.95)

0.91 (0.860.96)

0.87 (0.810.92)

DAS28 <2.6

0.84 (0.790.88)

0.88 (0.840.91)

0.85 (0.770.90)

0.90 (0.840.94)

DAS28 (CRP)<2.6

0.84 (0.790.88)

0.87 (0.840.90)

0.86 (0.790.92)

0.86 (0.800.91)

DAS28 (3var) <2.6

0.82 (0.780.86)

0.82 (0.780.86)

0.80 (0.720.87)

0.86 (0.790.91)

DAS28 (CRP/3var)<2.6

0.86 (0.820.90)

0.82 (0.780.86)

0.86 (0.790.92)

0.83 (0.760.89)

SDAI <3.30

0.26 (0.210.31)

0.99 (0.981.00)

0.30 (0.220.38)

0.99 (0.971.00)

CDAI <2.80

0.28 (0.240.34)

0.99 (0.971.00)

0.34 (0.260.42)

0.99 (0.971.00)

*Diagnosis Rheumatoid Arthritis according to the ACR classification criteria-1987